118

Treatment of Locally Advanced

Prostate Cancer

Maxwell V. Meng; Peter R. Carroll

Questions

1.Identification of patients with high-risk prostate cancer is best achieved by:

a.transrectal ultrasonography.

b.serum prostate-specific antigen (PSA).

c.digital rectal examination.

d.serum PSA, biopsy grade, clinical stage.

e.PSA kinetics.

2.By using the Kattan postoperative nomogram, which of the following contributes most to the risk of biochemical recurrence after radical prostatectomy?

a.Positive surgical margin

b.Pretreatment serum PSA of 17 ng/mL

c.Gleason 4 + 3 disease

d.Established capsular penetration

e.Seminal vesicle invasion

3.Neoadjuvant androgen deprivation (AD) before radical prostatectomy leads to:

a.improved biochemical-free survival.

b.improved overall survival.

c.reduced positive surgical margins.

d.reduced local recurrence.

e.increased operative morbidity.

4.In men with locally advanced prostate cancer undergoing prostatectomy, clinical overstaging (i.e., pathologically organ confined disease) occurs in:

a.less than 10%.

b.15% to 30%.

c.40% to 60%.

d.70% to 80%.

e.more than 90%.

5.The use of high-dose antiandrogen monotherapy after prostatectomy in men with locally advanced disease:

a.reduces disease progression.

b.increases cardiac morbidity.

c.does not have an impact on sexual function.

d.improves overall survival.

e.improves local disease control.

6.In men with locally advanced/high-risk prostate cancer, the most effective treatment among the following options is:

a.brachytherapy + external-beam radiation therapy.

b.neoadjuvant AD + external-beam radiation therapy.

c.neoadjuvant AD + external-beam radiation therapy + adjuvant AD.

d.concurrent AD plus external-beam radiation therapy.

e.long-term AD alone.

7.Risk assessment schemes for prostate cancer are most accurate for patients with:

a.low-risk disease.

b.high-risk disease.

c.the disease.

d.metastatic disease.

e.locally advanced cancers.

8.The current appropriate dose for adjuvant radiation therapy after radical prostatectomy is:

a.less than 45 Gy.

b.45 to 50 Gy.

c.51 to 55 Gy.

d.56 to 60 Gy.

e.greater than 60 Gy.

9.The use of AD in combination with radiation therapy for those with high-risk cancers is associated with all of the following EXCEPT:

a.improved local control.

b.improved biochemical-free survival.

c.less gastrointestinal toxicity.

b.enlarged lymph node.

c.recurrence in the prostatectomy bed.

d.rectal mass.

e.rectal diverticulum.

Answers

1.d. Serum PSA, biopsy grade, clinical stage. Although clinical stage, serum PSA, and Gleason score all individually predict pathologic stage and prognosis, the combination of these three variables increases the accuracy of this assessment.

2.b. Pretreatment serum PSA of 17 ng/mL. Despite the trend toward lower serum PSA at the time of diagnosis, PSA remains an important predictor of treatment failure, and greater elevations (greater than 8 ng/mL) of PSA contribute significantly to calculated biochemical recurrence.

3.c. Reduced positive surgical margins. The randomized and nonrandomized studies of neoadjuvant androgen deprivation in men with lower clinical stage (cT1-T2) clearly demonstrate a reduction in the rate of positive surgical margins; however, this advantage has not been observed in men with cT3c and has not translated into improved longterm PSA-free survival.

4.b. 15% to 30%. Recent data suggest that clinical overstaging occurs in approximately 27% of men with clinical stage T3 disease undergoing prostatectomy, consistent with the range in the literature of 7% to 26%.

5.a. Reduces disease progression. Bicalutamide at greater dose (150 mg) appears to have a positive effect in those men with locally advanced disease, with 43% reduction in disease progression and potential benefit of improved survival; however, it should be remembered that high-dose bicalutamide given to men with localized prostate cancer is associated with increased risk of death (hazard ratio: 1.23).

6.c. Neoadjuvant AD + external-beam radiation therapy + adjuvant AD. The accumulated data from multiple RTOG and EORTC trials suggests that improved outcomes are achieved with greater duration of administration of androgen deprivation in combination with externalbeam radiation therapy, with apparent benefit of both neoadjuvant and adjuvant therapy.

7.a. Low-risk disease. Validation has confirmed the general accuracy of the

available risk assessment tools, but there is a tendency to overestimate the risk of cancer recurrence in men with high-risk disease features.

8.e. Greater than 60 Gy. There is a trend to improve response to adjuvant radiation therapy and, most contemporary series report doses greater than

60 Gy, with potential threshold of either 61.2 or 64 Gy. Similarly, for primary radiation therapy, improved outcomes have been shown for higher doses

(78 Gy or greater).

9.c. Less gastrointestinal toxicity. The longer application (longer than 6 to 9

months) of AD in conjunction with radiation therapy may be associated with increased rectal morbidity as well as sexual dysfunction.

.e. All of the above. Data from European Organisation for Research and Treatment of Cancer (EORTC) 22911 and Southwest Oncology Group (SWOG) 8794 clearly demonstrate a benefit of adjuvant radiation therapy in men with pT3 disease, after radical prostatectomy, with respect to biochemical relapse-free, metastasis-free, and overall survival, as well as improved local control. The EORTC study suggests that patients who benefit the most are those with positive surgical margins.

Imaging

1.c. Recurrence in the prostatectomy bed. The pelvic CT scan demonstrates a mass in the prostatectomy bed on the right at the level of the urethra-vesicle anastomosis. Because the mass is anterior to the rectum, it is not likely to be a lymph node or seminal vesicle. In view of the radical prostatectomy specimen and the rising PSA, the mass is likely a prostate cancer recurrence in the prostatectomy bed.

Chapter review

1.At least 10% of men with newly diagnosed prostate cancer have locally advanced disease.

2.Risk assessment for locally advanced disease is best determined by a combination of PSA, T stage, cancer grade, and extent of cancer in the biopsy.

3.PSA recurrence following radical prostatectomy is influenced by Gleason score, extracapsular extension, seminal vesicle invasion, positive lymph nodes, and positive surgical margins.

4.Neoadjuvant androgen deprivation therapy before radical prostatectomy

has no role.

5.Early androgen deprivation therapy appears to have a potential survival advantage in subsets of men with more aggressive disease. Unfortunately, side effects of the therapy may be a sequela.

6.The role of adjuvant radiation therapy following radical prostatectomy is controversial. A subset of patients apparently benefits from adjuvant radiation therapy. Unfortunately, all studies to date are flawed such that specific subsets of patients who will benefit have not been adequately defined.

7.Patients with seminal vesicle involvement or regional lymph node metastases are highly likely to develop progressive disease despite adjuvant local therapy.

8.EORTC trials suggest that improved outcomes are achieved with greater duration of administration of androgen deprivation in combination with external-beam radiation therapy for selected patients with high-grade disease.